This proposal seeks to conduct FDA-required pre-clinical testing of a retinal prosthesis with penetrating electrodes designed and assembled by our team at Harvard Medical School and the Massachusetts Institute of Technology. Our retinal prosthesis is designed to restore vision to patients who are blind from either retinitis pigmentosa (RP) or age-related macular degeneration (AMD). There is no treatment to restore lost vision for either disease, although promising research in other fields also offers some hope of being able to help these patients. RP is the leading cause of inherited blindness in the world and is particularly devastating because it causes a slowly progressive loss of vision across the entire visual field of both eyes. AMD, which is the leading cause of blindness in the industrialized world, causes loss of central vision that robs a patient of being able to read or easily recognize faces. Our prosthetic system is composed of two components. The first component is a modified pair of glasses that contains an ultra-small camera that captures details of a visual scene; the glasses are connected to a cell phone-like device that processes the visual images. The digital visual signal and operating power are sent wirelessly to the second component of the prosthetic system, which is implanted around the back of the eye. The implanted component receives the visual signal and a custom-designed computer chip uses the incoming operating power to distribute electrical pulses to the retina. These electrical pulses will initiate nerve impulses tothe brain via the optic nerve. The primary goal of this prosthesis is to improve the quality-of-life of severely blind patients by enabling navigation in unfamiliar environments. Once achieved, the device also has the potential to facilitate other activities of daily living, like reading street sgns, addresses on buildings, bathroom designations (i.e. male vs. female), and finding and reaching accurately for glasses, plates, and utensils, among other things. The quality of vision that can be restored depends substantially upon the number of stimulation channels, or pixels. Our device has the largest number (256) of individually-controllable stimulation channels of any neural prosthetic device in the world. This relatively large number of stimulation channels should provide higher quality vision compared to the other devices. The penetrating electrodes should increase the safety of electrical stimulation and improve the quality of vision over what has been obtained with retinal prosthetic devices that use planar electrodes. Following completion of the work described in this grant proposal, our team would hope to receive an FDA approval to conduct a subsequent Phase I safety study of our retinal prosthesis with penetrating electrodes.